Page 107 - 85 cell signalling pathways

Cell Signalling Biology Michael J. Berridge Module 2 Cell Signalling Pathways 2 107

Module 2: Figure TGF-βR activation

Ligand trap (e.g. LAP, decorin)
TGF-
1

2 TGF-

P P P P MH1
Betaglycan 3 SARA
-SXSS-- MH2
Type II
receptors
Type I
receptors
SARA 4
Ser/Thr kinase domain 5
Glycine-serine-rich MH1
domain (GS) MH1 MH2 P P SARA
-SXSS-- MH2
-SXSS--
Smad2
GENE TRANSCRIPTION
(See Module 2: Figure Smad signalling) Smad3

Activation of the transforming growth factor β (TGF-β) receptor superfamily.
The transforming growth factor β (TGF-β) receptor superfamily uses the Smad signalling pathway to transmit information into the cell. The main
features of this pathway can be illustrated by considering the action of TGF-β, which activates the TGF-β receptor complex through a sequential
series of reactions as described in the text.

Module 2: Figure Smad signalling

TGF /activin/Nodal BMPs/GDFs

Smad4
P P
Smad2 Smad1
Smad3
Smad5
Smad8
P P

Coactivator/ Coactivator/
repressor P repressor
TGF /activin P BMP
TF TF
target genes target genes
SBE SBE

The Smad signalling pathway links cell-surface transforming growth factor β (TGF-β) receptors to gene transcription.
There are two main types of Smad signalling. In the one shown on the left, receptors activated by ligands such as transforming growth factor β (TGF-β),
activin and Nodal phosphorylate either Smad2 or Smad3. The phosphorylated Smads then heterodimerize with the co-mediator Smad (Co-Smad)
Smad4 to form a dimer that then translocates into the nucleus. Once in the nucleus, the Smad dimer then binds to a specific Smad-binding element
(SBE), which has a GTCT motif that is recognized by the MAD homology domain 1 (MH1).

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